By means of immunocytochemical staining, the canine pituitary intermediate lobe (IL) will be studied with respect to a) its postnatal ontogeny and b) the distinction of IL tumors associated with Cushing's disease from functionally similar tumors derived from the pars distalis (PD). Canine Cushing is a fairly common animal equivalent of human Cushing's disease. Since the latter is also said to occur in conjunction with two types of adenomas, those originating from PD corticotrophs and the other allegedly from corticotrophs invading the pars nervosa (PN) (which are regarded as the adult human's counterpart of the animal IL), attempts will be made to find, by immunostaining for a battery of pro-opiomelanocortin (POMC)-derivatives, reliable distinguishing characteristics between human PD and PN corticotrophs, which then should also differentiate between their adenomas, if these are indeed distinct entities. Plurihormonal adenomas are found with increasing frequency in human pituitaries. In the commonest among these, those containing growth hormone (GH) and prolactin, the two hormones may occur in identical cells. An investigation with immunogold staining is proposed to clarify whether these hormones are in the same or separate sets of secretory granules. For less common combinations of hormones in adenomas, such as GH and POMC derivatives, light microscopic immunostaining will have to be used to document the concurrence of two or more hormones in individual cells. If they are found together, colocalization in secretory granules will be investigated with immunogold staining. Numerous neuropeptides have been identified and/or immunocytochemically located in animal hypophyses. Their localization in the human hypophysis is unknown, but a necessary step in efforts to elucidate their functional significance in man. This will be attempted for such peptides as substance P, neurotensin, gastrin/cholecystokinin, vasoactive intestinal peptide, renin, angiotensin II and "brain-specific S-100 protein."